HSP110s exchange ATP for ADP on HSP70s:ADP

Stable Identifier
Reaction [transition]
Homo sapiens
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The substrate binding ability of heat-shock 70kDa proteins (HSP70s) is dependant on their bound state to either ATP or ADP. Release of a protein substrate is induced when HSP70s are bound to ATP and conversely, proteins substrates bind when HSP70s are bound to ADP. Intrinsic ATPase of HSP70s slowly hydrolyses ATP to ADP. This process can be speeded up by cochaperones such as HSP40s which stimulate ATPase activity. Nucleotide exchange factors (NEFs) regulate the lifespan of the HSP70:ADP:substrate complex by exchanging ADP for ATP, thus inducing the release of the substrate. Eukaryote NEFs include heat-shock protein 105kDa (HSPH1 aka HSP110) (Schuermann et al. 2008) and the BAG family molecular chaperone regulator (BAG) family (BAG1-5). BAGs inhibit the chaperone activity of HSP70s by promoting substrate release (Takayama et al. 1997, Takayama et al. 1999). HSC70-interacting protein (ST13 aka HIP) is a 48kDa tetrameric protein able to bind the ATPase domain of HSP70s and thought to stabilise the ADP state of HSP70s (Hohfeld et al. 1995, Prapapanich et al. 1996).

Literature References
PubMed ID Title Journal Year
9305631 BAG-1 modulates the chaperone activity of Hsp70/Hsc70

Xie, Z, Matsuzawa, S, Freeman, BC, Reed, JC, Morimoto, RI, Bimston, DN, Takayama, S, Aime-Sempe, C

EMBO J. 1997
8721986 Molecular cloning of human p48, a transient component of progesterone receptor complexes and an Hsp70-binding protein

Rimerman, RA, Chen, S, Smith, DF, Nair, SC, Prapapanich, V

Mol. Endocrinol. 1996
9873016 An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators

Xie, Z, Reed, JC, Takayama, S

J. Biol. Chem. 1999
7585962 Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle

Hartl, FU, Minami, Y, Höhfeld, J

Cell 1995
18550409 Structure of the Hsp110:Hsc70 nucleotide exchange machine

Morano, KA, Lafer, EM, Demeler, B, Taylor, AB, Gimenez, LE, Jin, S, Schuermann, JP, Cuellar, J, Valpuesta, JM, Wang, L, Sousa, R, Hart, PJ, Llorca, O, Jiang, J

Mol. Cell 2008
Catalyst Activity

adenyl-nucleotide exchange factor activity of HSP70 NEFs [cytosol]

This event is regulated
Negatively by
Orthologous Events
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